Can Adverse Neonatal Experiences Alter Brain Development and Subsequent Behavior?

Neonatology - Tập 77 Số 2 - Trang 69-82 - 2000
K.J.S. Anand1, Frank M. Scalzo
1Department of Pediatrics, University of Arkansas for Medical Sciences, and Pain Neurobiology Laboratory, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202-3591, USA.

Tóm tắt

Self-destructive behavior in current society promotes a search for psychobiological factors underlying this epidemic. Perinatal brain plasticity increases the vulnerability to early adverse experiences, thus leading to abnormal development and behavior. Although several epidemiological investigations have correlated perinatal and neonatal complications with abnormal adult behavior, our understanding of the underlying mechanisms remains rudimentary. Models of early experience, such as repetitive pain, sepsis, or maternal separation in rodents and other species have noted multiple alterations in the adult brain, correlated with specific behavioral phenotypes depending on the timing and nature of the insult. The mechanisms mediating such changes in the neonatal brain have remained largely unexplored. We propose that lack of N-methyl-<i>D</i>-aspartate (NMDA) receptor activity from maternal separation and sensory isolation leads to increased apoptosis in multiple areas of the immature brain. On the other hand, exposure to repetitive pain may cause excessive NMDA/excitatory amino acid activation resulting in excitotoxic damage to developing neurons. These changes promote two distinct behavioral phenotypes characterized by increased anxiety, altered pain sensitivity, stress disorders, hyperactivity/attention deficit disorder, leading to impaired social skills and patterns of self-destructive behavior. The clinical important of these mechanisms lies in the prevention of early insults, effective treatment of neonatal pain and stress, and perhaps the discovery of novel therapeutic approaches that limit neuronal excitotoxicity or apoptosis.

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Tài liệu tham khảo

10.1056/NEJM199409223311201

10.1016/0304-3959(94)90174-0

10.1016/S0140-6736(96)10316-0

10.1016/S0304-3959(98)00146-8

10.1001/archpsyc.56.3.215

10.1159/000013953

10.1056/NEJM199409223311201

10.1001/jama.276.6.453

10.1001/jama.272.11.853

10.1016/0304-3959(94)90128-7

10.1038/375325a0

10.1097/00002508-199712000-00008

10.1037//0735-7044.105.1.215

10.1016/0169-328X(93)90189-V

10.1073/pnas.95.9.5335

10.1038/37323

10.1016/0304-3959(93)90162-I

10.1016/0304-3959(92)90012-Z

10.1016/S0304-3959(98)00065-7

10.1097/00000542-199704000-00026

10.1016/0304-3959(96)03070-9

10.1016/0006-8993(89)90085-1

10.1016/S0896-6273(00)80433-X

10.1098/rspa.2000.0508

10.1016/S0304-3959(98)00184-5

10.1016/0306-4522(92)90193-6

10.1126/science.283.5398.70

10.1159/000017310

10.1016/0165-0173(90)90011-C

10.1038/6481

10.1016/0006-8993(89)90275-8

10.1073/pnas.93.10.4750

10.1016/S0301-0082(97)00067-1

10.1038/37601

10.1038/37605

10.1126/science.279.5356.1531

10.1126/science.277.5332.1659

10.1016/0387-7604(94)90025-6

10.1016/0165-6147(90)90184-A

10.1016/0031-9384(91)90422-K

10.1037//0735-7044.110.6.1435

10.1016/0091-3057(95)00196-4

10.1016/0006-8993(93)90374-V

10.1002/(SICI)1097-0185(199810)252:2<165::AID-AR2>3.3.CO;2-9

10.1038/4785

10.1038/7449

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Neonatology

Tập 77 Số 2

69-82

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